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Airborne polycyclic aromatic compounds contribute to the induction of the tumour-suppressing P53 pathway in wild double-crested cormorants
Ecotoxicology and Environmental Safety ( IF 6.8 ) Pub Date : 2017-12-22 , DOI: 10.1016/j.ecoenv.2017.12.028
S.J. Wallace , S.R. de Solla , P.J. Thomas , T. Harner , A. Eng , V.S. Langlois

Polycyclic aromatic compounds (PACs), including polycyclic aromatic hydrocarbons (PAHs) and PAH-like compounds are known or probable environmental carcinogens released into the environment as a by-product of incomplete combustion of fossil fuels and other organic materials. Studies have shown that exposure to PACs in the environment can induce both genotoxicity and epigenetic toxicity, but few studies have related PAC exposure to molecular changes in free ranging wildlife. Previous work has suggested that double-crested cormorants (Phalacrocorax auritus; DCCO) exhibited a higher incidence of genetic mutations when their breeding sites were located in heavily industrialized areas (e.g., Hamilton Harbour, Hamilton, ON, Canada) as compared to sites located in more pristine environments, such as in Lake Erie. The aim of this study was to determine if airborne PACs from Hamilton Harbour alter the tumour-suppressing P53 pathway and/or global DNA methylation in DCCOs. Airborne PACs were measured using passive air samplers in the Hamilton Harbour area and low-resolution mass spectrometry analysis detected PACs in livers of DCCOs living in Hamilton Harbour. Further hepatic and lung transcriptional analysis demonstrated that the expression of the genes involved in the DNA repair and cellular apoptosis pathway were up-regulated in both tissues of DCCOs exposed to PACs, while genes involved in p53 regulation were down-regulated. However, global methylation levels did not differ between reference- and PAC-exposed DCCOs. Altogether, data suggest that PACs activate the P53 pathway in free-ranging DCCOs living nearby PAC-contaminated areas.



中文翻译:

机载多环芳族化合物有助于诱导野生双冠cor中抑制肿瘤的P53途径

多环芳族化合物(PAC),包括多环芳族烃(PAH)和类PAH化合物,是已知的或可能的环境致癌物质,可能是化石燃料和其他有机材料未完全燃烧的副产物而释放到环境中。研究表明,暴露于环境中的PAC可以诱导遗传毒性和表观遗传毒性,但是很少有研究将PAC暴露与自由放养野生动物的分子变化相关。先前的研究表明,双冠cor(Ph); 与位于更原始环境(例如伊利湖)的地点相比,当其繁殖地点位于工业化程度较高的地区(例如加拿大安大略省汉密尔顿市的汉密尔顿港)时,DCCO)具有较高的遗传突变发生率。这项研究的目的是确定汉密尔顿港的机载PAC是否会改变抑制肿瘤的P53途径和/或DCCO中的整体DNA甲基化。使用被动空气采样器在汉密尔顿港地区测量了机载PAC,并通过低分辨率质谱分析检测了居住在汉密尔顿港的DCCO肝脏中的PAC。进一步的肝和肺转录分析表明,暴露于PACs的DCCOs的两个组织中,参与DNA修复和细胞凋亡途径的基因的表达均被上调,而参与p53调控的基因则被下调。但是,在暴露于参考和PAC的DCCO之间,总体甲基化水平没有差异。总体而言,数据表明,PACs在居住在PAC污染地区附近的自由散布的DCCO中激活P53途径。

更新日期:2017-12-22
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